The present invention relates generally to medical devices, systems, and methods for treating disease. More particularly, the invention relates to a system and method for achieving neuromodulation via an intravascular-delivered compound or drug.
Hypertension, or high blood pressure, affects a large proportion of the world's adult population. Renal, or renovascular, hypertension can be caused by hypoperfusion of the kidneys due to a narrowing of the renal arteries. The kidneys respond by giving off hormones that signal the body to retain salt and water, causing the blood pressure to rise. The renal arteries may narrow due to arterial injury or atherosclerosis. Despite effective drug regimens to regulate the renin-angiotensin-aldosterone pathway or to remove excess fluid from the body and reduce blood pressure, many patients with hypertension suffer from resistant forms of the disease.
Resistant hypertension is a common clinical problem, caused when a patient is unable to control high blood pressure by medication alone. Resistant hypertension is especially a problem in old and obese people. Both of these demographics are growing. While symptoms are not obvious in these patients, cardiovascular risk is greatly increased when they are unable to control their blood pressure.
The sympathetic nervous system (SNS) operates through a series of interconnected neurons that are part of both the peripheral and central nervous system. Through chemical synapses, the sympathetic nervous system is able to release chemical messengers that produce chemical chain reactions, which ultimately elicit physiologic responses. Therefore, messages traveling through the sympathetic nervous system can trigger changes in many bodily functions, including the up- and down-regulation of vascular tone (vasoconstriction and vasodilation, respectively). Vasoconstriction can be triggered by the release of Angiotensin I and its conversion into Angiotensin II. Angiotensin II directly causes the constriction of blood vessels, which then increases the systemic blood pressure. In certain situations, this increase in systemic blood pressure manifests itself in hypertension that can have a detrimental effect on numerous processes, including inhibiting blood flow to the kidneys, promotion of atherosclerosis, and stimulation of hypertrophy.
Hypertension is also caused by hyperactive renal sympathetic nerves. Renal sympathetic efferent and afferent nerves run generally longitudinally along the outside of arteries leading from the aorta to the kidneys. These nerves are critically important in the initiation and maintenance of systemic hypertension. It has been shown that by severing these nerves, blood pressure can be reduced.
Noting the strong correlation that exists between sympathetic nervous system function and many life threatening diseases, a strong suggestion exists that a potential therapy would be to control the activity of the sympathetic nervous system. Indeed, research has shown that stimulation of afferent nerves can have a profound affect on sympathetic activity and related blood pressure. Aars, et al., Reflex Changes in Sympathetic Activity and Arterial Blood Pressure Evoked by Afferent Stimulation of the Renal Nerve (1970). Furthermore, patent publications have disclosed catheter devices intended to ablate sympathetic nerves that otherwise innervate cardiac tissue, and furthermore that such ablation beneficially treats cardiac fibrillation, tachycardia, or cardiac arrhythmia. See for example U.S. Pat. No. 6,292,695 (issued 2001).
Percutaneous or endoscopic interventional procedures are very common in the United States and other countries around the world. Intravascular catheter systems are used for procedures such as balloon angioplasty, stent placement, atherectomy, retrieval of blood clots, photodynamic therapy, and drug delivery. All of these procedures involve the placement of catheters into arteries, veins, or other lumens of the body in order to provide access to the deep recesses of the body without the necessity of open surgery.
In cases where renal arterial occlusion is causing hypertension that cannot be controlled with medication, another potential therapy includes balloon angioplasty of the renal artery. In rare cases, surgical bypass grafting may be considered as a therapeutic alternative. While renal angioplasty can be effective in reducing blood pressure, angioplasty is plagued with resulting restenosis due to elastic recoil, dissection, and neointimal hyperplasia. Renal stents may improve the result, but also lead to restenosis or renarrowing of the artery due to neointimal hyperplasia.
While renal denervation had been performed with surgical methods in the past, more recently a catheter-based therapy to heat and destroy the nerves from within the renal artery using radio-frequency ablation has been studied.
While the use of catheter-based radiofrequency (RF) denervation appears to have a therapeutic effect, it is unknown what long-term implications will arise from the permanent damage caused to the vessel wall and nerves by the RF procedure. Radiofrequency energy denervates the vessel by creating heat in the vessel wall. The RF probe contacts the inner lining of the artery and the RF energy is transmitted through the tissue.
However, nerve ablation by catheter to disrupt sympathetic nervous system activity has its drawbacks. For example, ablation of the nerve bundles may be inconsistent or incomplete. Also, although catheterization is considered minimally invasive, it would be preferable to achieve therapy through non-invasive methods, such as through extracorporeal means. Furthermore, access to particular areas of the sympathetic nervous system may be difficult or impossible to achieve through catheterization, given that the sympathetic nervous system also exists outside of vascular walls in areas that a catheter cannot reach.
For all of these reasons, it would be desirable to provide additional and improved systems and methods for delivery into the adventitial/perivascular/periarterial space of the renal arteries, sympatholytic or sympathetic nerve blocking agents, including other agents that can modulate nerve function, to accomplish biological and reversible denervation while not creating injury to the blood vessel or aggravating the underlying vascular disease. As a result, there is a need for a means of disrupting sympathetic nervous system afferent and efferent activity in a non-invasive manner that allows any location of the sympathetic nervous system to be targeted for therapy.
In a further aspect of the prior art, systems are known for injecting drugs and agents into a patient from deep within the vascular anatomy of the patient. Typically, these systems will locate the catheter at a fixed position within the radial center of a vessel using inflatable or expandable means, and a needle will be advanced to protrude from the catheter and penetrate the tissue of the vascular wall. A problem with such prior art systems is that a physician typically has difficulty determining how deep into the tissue the needle has advanced. This problem arises because the needle must first advance radially a certain distance from the catheter and through the space in the vessel before it reaches the vessel wall. Depending on the local anatomy of the vessel, this distance is not predictable, and cannot be seen with adequate precision using fluoroscopic methods. Thus, even if a physician knows exactly how far the needle tip has extended from an external wall of the catheter, she cannot assess how far the tip has penetrated into tissue because the distance between the catheter and the vessel wall is unknown.
As a result, there is a need in the art for an injection catheter that may be used to insert a needle into the vascular wall by a distance that it precisely known by the physician. This invention addresses these and other needs.